1. Field of the Invention
The present invention relates to preparation of microparticles. More particularly, the present invention relates to a method and an apparatus for preparing microparticles having a selected polymer molecular weight.
2. Related Art
A variety of methods is known by which compounds can be encapsulated in the form of microparticles. It is particularly advantageous to encapsulate a biologically active or pharmaceutically active agent within a biocompatible, biodegradable wall forming material (e.g., a polymer) to provide sustained or delayed release of drugs or other active agents. In these methods, the material to be encapsulated (drugs or other active agents) is generally dissolved, dispersed, or emulsified, using stirrers, agitators, or other dynamic mixing techniques, in one or more solvents containing the wall forming material. Solvent is then removed from the microparticles and thereafter the microparticle product is obtained.
One variable that affects the in vitro and in vivo performance of the microparticle product is the molecular weight of the polymer or polymeric matrix material in the final microparticle product. Molecular weight affects drug release characteristics. The molecular weight of a polymer influences the biodegradation rate of the polymer. For a diffusional mechanism of active agent release, the polymer should remain intact until all of the active agent is released from the microparticles, and then degrade. The active agent can also be released from the microparticles as the polymeric matrix material bioerodes. By an appropriate selection of polymeric materials a microparticle formulation can be made in which the resulting microparticles exhibit both diffusional release and biodegradation release properties. This is useful in affording multiphasic release patterns.
It has been reported that the molecular weight of the poly(D,L-lactide) ("DL-PL") component of microcapsules containing up to 50% thioridazine free base decreased during fabrication, and in dissolution rate studies of the microcapsule (see Maulding, H.V. et al., Biodegradable Microcapsules: "Acceleration of Polymeric Excipient Hydrolytic Rate by Incorporation of a Basic Medicament", Journal of Controlled Release, Volume 3, 1986, pages 103-117; hereinafter "the Maulding article"). The results reported in the Maulding article reveal that the degradation rate of DL-PL in ketotifen free base microcapsules was greater when the encapsulation process was carried out at 4.degree. C. than it was when the encapsulation process was carried out at 25.degree. C. In contrast, the degradation rate of DL-PL in thioridazine free base microcapsules was greater when the encapsulation process was carried out at 23.degree. C. than it was when the encapsulation process is carried out at 4.degree. C. Based on these results, the Maulding article suggests circumventing the polymer degradation by carrying out the preparation of microcapsules at 4.degree. C. in the case of thioridazine base. The Maulding article does not provide a method by which the molecular weight of the polymer in the finished microparticle can be conveniently controlled. Nor does the Maulding article provide a method for preparing microparticles that have a selected polymer molecular weight in the finished microparticle product.
Thus, there is a need in the art for an improved method for preparing microparticles that controls the molecular weight of the polymer or polymeric matrix material in the finished microparticle product. There is a particular need in the art for an improved process that provides a method for preparing microparticles that have a selected polymer molecular weight. The present invention, the description of which is fully set forth below, solves the need in the art for such an improved method.